This research project is concerned with an intensive investigation of the enzymes classified as cyclic nucleotide phosphodiesterases. A variety of isoenzymes possessing the activity to hydrolyze cyclic 3',5' adenosine monophosphate (cyclic AMP) and/or cyclic 3', 5' guanosine monophosphate (cyclic GMP) have been identified in mammalian tissue preparations. These enzymes vary in their physical properties, catalytic properties, and tissuedistribution. The pivotal position of cyclic nucleotides as second messenger in the control of cellular activity and in the response to many hormones (epinephrine, glucagon, ACTH, insulin and others) makes it of critical importance that the enzyme involved in their degradation be completely understood. This investigation of cyclic nucleotide phosphodieterase will include the following: 1) Enzyme separation and purification, 2) Physical characterization, 3) Kinetic analysis, 4) Regulation analysis, 5) Drug response survey, 6) Integration into physiological models. The biochemical information obtained will be invaluable to the pharmacologist, the endocrinologist and, eventually, the physician.